Yersinia pestis is a gram-negative bacterium that is the etiological agent of plague, and is a potential bioterrorism agent. There are three forms of the human disease: bubonic, septicemic, and pneumonic (Perry et al., Clin. Microbiol. Rev., 10: 35-66 (1997), and Ingelsby et al., JAMA, 283: 2281-2290 (2000)). Pneumonic plague is of most concern as a biological threat due to its rapid onset, high mortality, and rapid spread. While antibiotics can be used to treat plague, the fatality rate is high when treatment is delayed more than 24 hours after the onset of disease symptoms (Perry et al., supra, and Smego et al., Eur. J. Clin. Microbiol. Infect. Dis., 18: 1-15 (1999)).
No vaccines against plague are currently available in the United States. Several vaccines have been developed, including killed whole-cell formulations and the live EV76 vaccine (Titball et al., in Plotkin et al., eds., Vaccines, WB Saunders, Philadelphia, p. 999 (2004), Russell et al., Vaccine, 13: 1551-1556 (1995), Titball et al., Vaccine, 19: 4175-4184 (2001), and Titball et al., Expert Opin. Biol Ther., 4: 965-973 (2004)). While these vaccines have been tested in humans, they offer low levels of protection, have numerous side effects, and require frequent immunizations with consequent prolonged time to develop immunity.
Vaccines based on the virulence (V) antigen of Y. pestis also have been developed, including subunit and DNA vaccines. Immunization with a subunit vaccine against V antigen provides protection against plague in mice (Anderson et al., Infec. Immun., 64: 4580-4585 (1996), Leary et al., Infect. Immun., 63: 2854-2858 (1995), Green et al., FEMS Immunol. Med. Microbiol., 23: 107-113 (1999), Motin et al., Infect. Immun., 62: 192-201 (1994), Bennett et al., Vaccine, 18: 588-596 (1999), and Williamson et al., Vaccine, 20: 2933-2941 (2002)). DNA vaccines based on V antigen elicit low antibody titers, and protection against Y. pestis challenges is reached only after several immunizations (Wang et al., Vaccine, 22: 3348-3357 (2004)).
Accordingly, there remains a need for alternative compositions and methods for protection against Y. pestis infection that elicit a rapid and efficient immune response in a broad spectrum of the population. The invention provides such a composition and method. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.